12-56247720-G-A

Position:

• chr12-56247720-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173595.4(ANKRD52):​c.2033C>T​(p.Ala678Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD52 NM_173595.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

ANKRD52 (HGNC:26614): (ankyrin repeat domain 52)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10978466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD52	NM_173595.4	c.2033C>T	p.Ala678Val	missense_variant	19/28	ENST00000267116.8	NP_775866.2
ANKRD52	XM_017019183.2	c.2030C>T	p.Ala677Val	missense_variant	18/27		XP_016874672.1
ANKRD52	XM_011538197.3	c.1850C>T	p.Ala617Val	missense_variant	18/27		XP_011536499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD52	ENST00000267116.8	c.2033C>T	p.Ala678Val	missense_variant	19/28	1	NM_173595.4	ENSP00000267116.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.2033C>T (p.A678V) alteration is located in exon 19 (coding exon 19) of the ANKRD52 gene. This alteration results from a C to T substitution at nucleotide position 2033, causing the alanine (A) at amino acid position 678 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.30	T
Sift4G	Benign	0.22	T
Polyphen		0.0060	B
Vest4		0.24
MutPred		0.49		Gain of catalytic residue at D682 (P = 0.0348);
MVP		0.31
MPC		0.81
ClinPred		0.30	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56641504;